Patient-controlled bolus femoral nerve block after knee arthroplasty: quadriceps recovery, analgesia, local anesthetic consumption.

BACKGROUND: Continuous femoral nerve block (cFNB) induces quadriceps muscle weakness, but patient-controlled femoral nerve block (PCFNB) can provide analgesia with lower consumption of local anesthetics compared to cFNB. We hypothesized that cFNB followed by PCFNB leads to accelerated recovery of quadriceps weakness after total knee arthroplasty compared to cFNB alone. Secondary outcomes were local anesthetic consumption, pain, and mobilization. METHODS: Fifty-six subjects received post-operative cFNB for 24 h and then randomized to receive either cFNB (basal infusion of 6 ml/h using a dummy bolus button; n = 27) or PCFNB (bolus infusion of 3 ml with a lockout time of 30 min and no basal infusion; n = 29) using 0.08% levobupivacaine for the subsequent 24 h in a double-blind manner (registration: UMIN000010105). Quadriceps strength was assessed using a hand-held dynamometer. The percentage change from baseline was compared between groups. RESULTS: Quadriceps strength at 48 h was 47.3 ± 18.3% in the cFNB group and 49.7 ± 15.7% in the PCFNB group (95% confidence interval -7.0-11.9%, P = 0.61). Local anesthetic consumption during the post-operative period was significantly lower in the PCFNB group compared to the cFNB group (102 ± 10.8 ml vs.146 ± 4.6 ml; P < 0.001). No significant differences were found in any of the other outcomes, including pain scores at rest and during knee rehabilitation. CONCLUSION: Continuous femoral nerve block followed by PCFNB does not improve quadriceps strength recovery time compared to cFNB alone after total knee arthroplasty, but similar analgesic effects were demonstrated with reduced levobupivacaine consumption.

Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?

We found that congenital uterine anomalies have a negative impact on reproductive outcome in recurrent-miscarriage couples, being associated with further miscarriage with a normal embryonic karyotype. There has been no study comparing live birth rates between patients with and without surgery. We conducted a prospective study to prove that surgery for a bicornuate or septate uterus might improve the live birth rate. A total of 170 patients with congenital uterine anomalies suffering two or more miscarriages were examined. The live birth rate after ascertainment of anomalies, cumulative live birth rate and infertility rate, were compared between patients with and without surgery. In patients with a septate uterus, the live birth rate (81.3%) at the first pregnancy after ascertainment of anomalies with surgery tended to be higher than that (61.5%) in those without surgery. The infertility rates were similar in both groups, while the cumulative live birth rate (76.1%) tended to be higher than without surgery (60.0%). Surgery showed no benefit in patients with a bicornuate uterus for having a baby, but tended to decrease the preterm birth rate and the low birth weight. The possibility that surgery has benefits for having a baby in patients with a septate uterus suffering recurrent miscarriage could not be excluded.

Inhibition of FKBP rotamase activity by immunosuppressant FK506: twisted amide surrogate.

The immunosuppressive agents cyclosporin A and FK506 inhibit the transcription of early T cell activation genes. The binding proteins for cyclosporin A and FK506, cyclophilin and FKBP, respectively, are peptidyl-prolyl-cis-trans isomerases, or rotamases. One proposed mechanism for rotamase catalysis by cyclophilin involves a tetrahedral adduct of an amide carbonyl and an enzyme-bound nucleophile. The potent FKBP rotamase inhibitor FK506 has a highly electrophilic carbonyl that is adjacent to an acyl-pipicolinyl (homoprolyl) amide bond. Such a functional group would be expected to form a stabilized, enzyme-bound tetrahedral adduct. Spectroscopic and chemical evidence reveals that the drug interacts noncovalently with its receptor, suggesting that the alpha-keto amid of FK506 serves as a surrogate for the twisted amide of a bound peptide substrate.

Electro-optic probe measurements of electric fields in plasmas.

The direct measurements of high-frequency electric fields in a plasma bring about significant advances in the physics and engineering of various waves. We have developed an electro-optic sensor system based on the Pockels effect. Since the signal is transmitted through an optical fiber, the system has high tolerance for electromagnetic noises. To demonstrate its applicability to plasma experiments, we report the first result of measurement of the ion-cyclotron wave excited in the RT-1 magnetosphere device. This study compares the results of experimental field measurements with simulation results of electric fields in plasmas.

Accumulation of advanced glycation end products in women with preeclampsia: possible involvement of placental oxidative and nitrative stress.

Advanced glycation end products (AGEs) are known to cause oxidative damage in various cells by binding with its receptor, RAGE. We measured the serum level of AGEs and examined the AGEs, RAGE, and the other biomarkers of oxidative stress in the placentas from preeclamptic women. Competitive ELISA was carried out to measure the AGEs in serum. Western blotting was performed to analyze AGEs and RAGE in the placenta. Immunohistochemical analyses were performed to examine the localization of AGEs, RAGE, and other biomarkers of oxidative stress in the placenta. The mean level of serum AGEs in preeclamptic women was significantly higher than that in healthy non-pregnant women or healthy pregnant women. Western blotting revealed that the level of AGEs or RAGE in preeclamptic placenta was significantly higher than that in normal placenta. Immunohistochemical analyses showed that levels of nitrotyrosine and nitroguanosine, which are formed by reactive nitrogen species, in preeclamptic placenta were higher than those in normal placenta. Accumulation of 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine indicated enhanced oxidative modifications of lipids and DNA in preeclamptic placenta. The AGE-RAGE system, which is upregulated in preeclampsia, is likely to be involved in the oxidative stress of preeclampsia.

Isolation and characterization of the distal promoter region of mouse Cbfa1.

Cbfa1 is an essential transcription factor for bone formation, and as such little is known about the region responsible for the transcriptional regulation of this gene. Here we report the determination of the transcription start sites, isolation and partial characterization of distal promoter region of this gene. Three transcription start sites were identified by the 5'-Cap site method, recently invented for rapid examination of the 5'-end of genes of interest. A reporter construct containing 1.8 kb of 5' of transcription start sites had approximately 25-fold more luciferase activity than the promoter-less vector in osteoblastic cell lines. Deletion analysis of the reporter construct demonstrated that the minimal region to express promoter activity lies between bp -168 and -99, taking the most downstream transcription start site as +1. By Northern blot analysis, mRNA expression from the distal promoter was detected in the differentiated osteoblastic cell lines, UMR-106, ROS17/2.8 and MC3T3-E1, but not in cell lines of immature phenotype or originated from other organs. Luciferase activity was strongest in UMR-106 and ROS17/2.8, and weakest in COS-1 and HepG2, which are cell lines originating from other organs, corresponding to the level of mRNA expression. These results demonstrated that the distal promoter region examined here is important for tissue- and cell-type-specific gene expression of Cbfa1.

Cloning of rabbit TR4 and its bone cell-specific activity to suppress estrogen receptor-mediated transactivation.

To clone a new nuclear receptor, we screened a rabbit heart complementary DNA (cDNA) library with degenerate oligonucleotide probes corresponding to the DNA-binding domain of nuclear receptors, which is highly conserved among receptors. One of the cDNA clones, clone 23, encodes a novel protein of 596 amino acids, and predicted molecular mass is 66 kDa. Homology search analysis identified this protein as rabbit TR4 (TR4-0). We also cloned the cDNA encoding a rabbit TR4 isoform (TR4-1), which lacks the putative C-terminal ligand-binding domain (350 amino acids) caused by a 23-bp exon deletion, which probably occurred during messenger RNA (mRNA) splicing. Northern blot analysis showed that TR4s are expressed with two kinds of mRNAs (9.0 kb and 2.8 kb), both of which are relatively abundant in brain, testis, and bone. RT-PCR analysis, using pairs of primers specific for each TR4, showed that both types of receptor express in various tissues. Furthermore, both are present in primary osteoblasts and bone marrow cells, though the mRNA levels of TR4-0 were much higher than those of TR4-1. A functional study, using a transient transfection assay, showed that both receptors suppressed retinoid X receptor (RXR)-retinoid acid receptor, RXR-TR, and RXR-VDR-mediated transactivation significantly in COS-1 and osteosarcoma cells (UMR-106, ROS17/2.8) and that TR4-0 was much more effective than TR4-1. Unexpectedly, we found that the TR4s effectively suppressed estrogen receptor-mediated transactivation in bone cells, but neither in kidney (COS-1) nor breast cancer cells (MCF-7, one of the major target cells of the estrogen action). Thus, the present study shows a novel property of the TR4 orphan receptor, acting as a bone cell-specific repressor in the estrogen receptor-mediated signaling pathway.

Cloning of mouse FGF10 and up-regulation of its gene expression during wound healing.

We cloned the mouse homolog of FGF10, which was recently reported as a new member of the FGF family. The predicted molecular mass of this molecule is 23.6 kDa, and both nucleotide and amino acid sequences show high degrees of similarity with those of the rat. Examination of mouse FGF10 mRNA expression in various tissues and developmental stages by Northern hybridization revealed tissue- and developmental stage-specific expression of the gene. Similarly to the rat counterpart, mouse FGF10 mRNA (4.5 kb) was expressed relatively abundantly in embryos and the lung, and at much lower levels in brain and heart. In addition, a shorter transcript (1.3 kb) is expressed only in testis. Considering the high similarity in primary structure between FGF10 and FGF7 (known as keratinocyte growth factor; KGF), we also examined the gene expression of FGF10 during wound healing using a mouse model. FGF10 mRNA was highly induced 1 day after injury and decreased rapidly by 3 days. This suggests that FGF10 is a primary factor in the process of wound healing similarly to other growth factors such as TGF alpha and FGF7.

Increased intra-abdominal pressure and cardiac filling pressures in obesity-associated pseudotumor cerebri.

OBJECTIVES: To determine whether intra-abdominal pressure (as estimated from urinary bladder pressure) is elevated in patients with central obesity (as measured by sagittal abdominal diameter) and pseudotumor cerebri and whether this increased intra-abdominal pressure is associated with increased pleural pressure and cardiac filling pressure, implying a resistance to venous return from the brain. DESIGN: Nonrandomized, prospective. SETTING: University hospital, operating room. MAIN OUTCOME MEASUREMENTS: Intracranial pressure, urinary bladder pressure, sagittal abdominal diameter, transesophageal pleural pressure, central venous pressure, pulmonary artery pressure, and pulmonary artery occlusion pressure. SUBJECTS: Six women with pseudotumor cerebri (one with CSF leak, one with lumboperitoneal shunt). RESULTS: Urinary bladder pressure (22 +/- 3 cm H2O) and sagittal abdominal diameter (29 +/- 3 cm) were significantly elevated in these patients with elevated intracranial pressure (293 +/- 80 mm H2O) compared with a previously reported group of nonobese control patients. The transesophageal pleural pressure (15 +/- 10 mm Hg), central venous pressure (20 +/- 6 mm Hg), mean pulmonary artery pressure (31 +/- 6 mm Hg), and pulmonary artery occlusion pressure (21 +/- 7 mm Hg) were all markedly elevated compared with published normal values and with previous data from obese patients without pseudotumor cerebri. CONCLUSIONS: These data support the hypothesis that central obesity raises intra-abdominal pressure, which increases pleural pressure and cardiac filling pressure, which impede venous return from the brain, leading to increased intracranial venous pressure and increased intracranial pressure associated with pseudotumor cerebri.

Quantification of area at risk in acute myocardial infarction by tomographic imaging.

UNLABELLED: The purpose of this study was twofold: to validate, in a phantom heart model, a simple threshold technique for the quantification of defect size using 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) imaging and to compare, in patients with acute myocardial infarction, defect size as shown by BMIPP imaging, with the extent of severe hypokinesis shown by left ventriculography. METHODS: In a phantom study, defect size was calculated using a standard geometric formula. In a clinical study, BMIPP imaging was performed in 20 patients 10 +/- 5 days after the onset of their infarction. Using the centerline method, the area at risk was defined by contrast ventriculography as the percentage of chords with wall motion >2 s.d. below normal. RESULTS: In the phantom study, a threshold value of 60% yielded the best agreement between true and measured defect size. In the clinical study, the defect size shown by BMIPP imaging was greater in anterior than in inferior infarcts (p < 0.001) and correlated well with the risk area revealed by contrast ventriculography (r = 0.80, p < 0.0001) CONCLUSION: The above preliminary data, admittedly from a small group of patients, suggest that tomographic BMIPP imaging provides an accurate quantification of defect size by means of a simple threshold technique and, in the subacute phase, permits determination of the amount of myocardium at risk after acute myocardial infarction.

Multisegmented kinoform phase plate for spatial and temporal control of the focal-plane irradiance profile.

Kinoform phase plates (KPPs) are widely used in inertial confinement fusion to improve energy efficiency and to produce an optimum irradiance profile on the target plane. However KPPs are sensitive to beam aberrations and offer little flexibility in temporally tailoring the far-field pattern. To overcome these problems, we developed a multisegmented KPP and demonstrated temporal control of a focusing pattern and protection against phase distortions by numerical simulations.

Laguerre-Gaussian beam generated with a multilevel spiral phase plate for high intensity laser pulses.

We investigated an Laguerre-Gaussian (LG) beam that can carry an orbital angular momentum and has a doughnut-shaped intensity pattern. We developed a multilevel spiral phase plate (SPP) that generates an LG beam by applying the wave surface of a spiral structure directly to a Gaussian beam for application to microscopic laser material processing.We experimentally demonstrate, for the first time, that it is possible to generate an LG beam with the multilevel SPP that allows the use in high intensity laser pulses.

Blood flow study of meningothelial and fibrous meningiomas by xenon-CT.

Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (< 32 mm) and there was little or no peritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow(TBF) and the contralateral tissue blood flow(CLBF) were determined. The ratio of these parameters(TBF/CLBF) was 1.753 +/- 0.467 for meningothelial meningiomas and 0.809 +/- 0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. The small meningothelial and fibrous meningiomas with little effect on the surrounding brain tissue could be distinguished from each other by xenon-enhanced computed tomography.

Exercise-induced silent myocardial ischemia in single vessel coronary artery disease associated with Q wave infarction. Assessment by thallium 201 single-photon emission computed tomography.

PURPOSE: To examine the relationship between the symptom of ischemia and the amount of abnormally perfused myocardium, coronary arteriography and exercise and redistribution thallium 201 single-photon emission computed tomography (SPECT) were analyzed. MATERIALS AND METHODS: The study group consisted of 153 patients with single-vessel coronary artery disease; 53 patients had no pathologic Q waves (group 1) and 100 patients had pathologic Q waves consistent with the area supplied by the diseased vessel (group 2). Twenty normal subjects were used as control subjects. The apical, mid, and basal left ventricular levels of the short-axis view and apical portion of the long-axis view were divided into 20 segments, and segmental images were scored blindly on a 0 (normal) to 4 (severely reduced uptake) scale. The redistribution score was defined as the thallium 201 defect score of exercise subtracted from that of the redistribution image and was used as a measure of the amount of ischemic myocardium. RESULTS: The redistribution score in 20 control subjects was 0.20 +/- 2.06, and the upper limit of normal redistribution score was defined as mean + 2 x SD (4.32). In group 1, 40 of 53 patients had a redistribution score above the normal range. In group 2, 34 of 100 patients had a redistribution score above the normal range. Of 40 patients in group 1, angina during exercise was observed in 22 patients (55 percent). Twenty-two patients who had angina had a redistribution score of 15.2 +/- 6.7, while those who did not have angina had a score of 13.7 +/- 5.2 (p = NS). Of 34 patients in group 2, angina was observed in 10 patients (29 percent) during exercise. Ten patients with angina had a redistribution score of 10.1 +/- 4.4, and those without angina had a score of 9.9 +/- 3.4 (p = NS). CONCLUSION: Thus, the incidence of silent ischemia without the Q wave infarct zone was found to be higher than that within the ischemic zone without Q wave. Patients with silent and symptomatic ischemia during exercise have similar amounts of ischemic myocardium demonstrated by tomographic thallium 201 imaging; this was found in patients who had Q wave infarction and in those who did not.

Antiviral and immunomodulating activities of chemically synthesized lipid A-subunit analogues GLA-27 and GLA-60.

Biological and antiviral activities of chemically synthesized lipid A-subunit analogues, GLA-27 and GLA-60, were investigated with respect to defense mechanisms such as macrophage and natural killer (NK) cell activation and interferon (IFN)-inducing activity. GLA-27, a 4-O-phosphono-D-glucosamine derivative carrying 3-O-tetradecanoyl (C14) and 2-N-3-tetradecanoyloxytetradecanoyl (C14-O-(C14] group, and GLA-60, a similar analogue carrying 3-O-linked C14-O-(C14) and 2-N-linked 3-hydroxytetradecanoyl (C14-OH) groups, strongly inhibited the formation of pox tail lesions and the growth of vaccinia virus at the tail lesion sites in infected mice. The antiviral activity of GLA-60 was about 1000-fold higher than that of muramyldipeptide (MDP), a representative immunomodulator. GLA-27 and GLA-60 had stronger immunomodulating activity than MDP in macrophage activation, NK cell activation and IFN-inducing activity, although it was weaker than natural lipid A. Toxic manifestations such as pyrogenicity, local Schwartzman reaction and lethality were far less pronounced for GLA-27 and GLA-60 than for natural lipid A.

Enhancement of nonspecific resistance to viral infection by chemically synthesized lipid A-subunit analogs with different backbone structures and acyl groups.

Protection against vaccinia virus infection and induction of interferon (IFN) were investigated in Propionibacterium acnes-primed mice following treatment with chemically synthesized lipid A-subunit derivatives. The antiviral activity was based on the reduction of numbers of tail lesions in mice injected intravenously with the test compounds 1 day before virus infection. GLA-27, a 4-O-phosphono-D-glucosamine carrying 3-O-tetradecanoyl (C14) and N-3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups, offered significant antiviral activity. Chemical modifications at the C1 position of GLA-27, e.g. phosphorylation, replacement of OH by an SH, did not cause a significant change in antiviral activity. GLA-57 carrying an N-3-dodecanoyloxytetradecanoyl group showed stronger activity than GLA-27, but GLA-58 carrying an N-3-hexadecanoyloxytetradecanoyl group did not exhibit significant activity. GLA-59 carrying 3-O-3-hydroxytetradecanoyl and N-C14-O-(C14) groups was more active than GLA-27 and GLA-57. GLA-60 possessing the same fatty acid substituents as GLA-59 but in the reversed order was the most active of all compounds tested. This suggests that the nature and position of the acyl substituents are important for achieving the antiviral effects. The (R) isomers of GLA-59 and GLA-60 possessed stronger IFN-inducing activity than the (S) isomers, but no significant difference in antiviral activity was seen between the isomers.

Structure-activity relationship of lipid A: comparison of biological activities of natural and synthetic lipid A's with different fatty acid compositions.

To investigate the structure-activity relationships, various biological activities, including pyrogenicity, lethal toxicity, elicitation of Shwartzman reaction, mitogenicity and tumor necrosis factor (TNF)-inducing activity, were compared among natural and synthetic lipid A's differing in fatty acid composition. In all these tests, natural lipid A's from Escherichia coli and Salmonella minnesota and synthetic LA-15-PP, which carries 3-hydroxy- and 3-acyloxy-tetradecanoyl groups at the 2, 3 and 2', 3' positions, respectively, showed the strongest activities among the tested lipid A's. In contrast, LA-16-PP, in which the amide-bound 3-hydroxytetradecanoic acid at position 2 of LA-15-PP is replaced by 3-hexadecanoyloxytetradecanoic acid, exhibited lower activity than LA-15-PP and natural lipid A's. Although LA-16-PP has been assumed to have a typical Salmonella lipid A structure (and, in fact, it has a structure corresponding to one of the components of Salmonella lipid A), the activity of this synthetic compound was not comparable to that of natural Salmonella lipid A. LA-17-PP, in which tetradecanoic acid is the sole fatty acid component, exhibited relatively strong mitogenicity and TNF-inducing activity, but very low pyrogenicity. The activities of LA-18-PP, which has ester-bound tetradecanoic acid and amide-bound 3-hydroxytetradecanoic acid, were lower than those of LA-17-PP. The results indicate that the differences in fatty acid composition of lipid A's have important influences on the biological activities studied.

p53-independent transient p21(WAF1/CIP1) mRNA induction in the rat brain following experimental traumatic injury.

The expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) mRNA after traumatic brain injury in rats was investigated using an in situ hybridization technique, along with regulating gene p53 and stress response gene hsp70 mRNA levels. At 3 h postinjury, p21(WAF1/CIP1) mRNA was markedly increased in the cortex, white matter, thalamus, CA2, a part of CA1,3 and dentate gyrus of the injured side. Hybridization signals remained elevated at 6 h in injured cortex and hippocampus and returned to the baseline by 24 h post-insult. On the other hand, p53 mRNA induction was not observed in any brain sections throughout the post-injury time course. Slight expression of hsp70 mRNA was detected in the injured cortex 3-6 h following injury and this was similar to the temporary pattern of p21(WAF1/CIP1) mRNA expression. This study showed p21(WAF1/CIP1) mRNA to be transiently induced after traumatic brain injury, independent of p53, this possibly being an early stress response to protect cells by arresting them in the cycle and allow DNA repair.

1988: unilateral high-frequency jet ventilation during one-lung ventilation for thoracotomy. Updated in 1995.

One-lung ventilation is indicated during thoracic operations for bronchopleural fistula, pulmonary abscess, and pulmonary hemorrhage in spite of the possibility of the development of severe hypoxemia. To evaluate methods for improving oxygen transport during one-lung ventilation, we applied high-frequency jet ventilation (HFJV) and continuous positive airway pressure (CPAP) to the nondependent lung following deflation to atmospheric pressure in each procedure, and measured the effects on cardiac output and arterial oxygenation. In each case, the dependent lung was ventilated with conventional intermittent positive pressure ventilation (IPPV). Eight patients were studied during posterolateral thoracotomy using double-lumen endobronchial tubes. HFJV or CPAP to the nondependent lung improved arterial oxygenation significantly during both closed and open stages of the surgical procedures (p < 0.008). When the chest was open, HFJV maintained satisfactory cardiac output, whereas CPAP usually decreased cardiac output (p < 0.008). There were no significant differences in mean partial pressure of arterial carbon dioxide between HFJV, CPAP, and deflation to atmospheric pressure. In conclusion, HFJV to the nondependent lung provides not only satisfactory oxygenation but also good cardiac output, thereby maintaining better oxygen transport than CPAP or deflation to atmospheric pressure, while the dependent lung is ventilated with IPPV during one-lung ventilation for thoracotomy.

Right ventricular function and high-frequency positive-pressure ventilation during coronary artery bypass grafting.

The hemodynamic and respiratory consequences of two modes of ventilation, conventional intermittent positive-pressure ventilation with a frequency of 10 cycles/min and high-frequency positive-pressure ventilation at 70 cycles/min were investigated before and after cardiopulmonary bypass in 6 patients having coronary artery bypass grafting. All patients were adequately ventilated with each mode. During prebypass and postbypass periods, the group with high-frequency ventilation had significantly lower peak airway pressures (p = 0.0001) and mean airway pressure (p less than 0.05). There were, however, no significant differences in right ventricular performance or pulmonary vascular resistance between the two modes of ventilation. No significant differences in other cardiovascular and respiratory variables were noted. High-frequency positive-pressure ventilation, with the advantage of quieter operating conditions and improved surgical access, can be safely applied when meticulous operation or hemostasis is required or during dissection of the internal mammary artery.